Tumors derived from F1 hybrids between two H-2 congenic lines, when transplanted into the parental lines produce variants that are selectively compatible with one but incompatible with the other parent. The parental tumor variants can be shown to have lost H-2 antigens indigenous to the incompatible parent. This application proposes to study the mechanism of variant formation at both the genotypic and phenotypic levels. Recently developed chromosme markers and the improved techniques of karyological analysis will be used to determine whether variant formation is accompanied by specific chromosome loss or gross structural rearrangements of the H-2 bearing chromosome. The possibility will be explored of using extenal markers on both sides of the H-2 complex for signaling the genetic events occurring during variant formation. The role in the variant formation of the different H-2 regions will be studied using congenic H-2 recombinant strains. Particular attention will be paid to the I region of the H-2 complex. The loss of individual H-2 antigens will be reinvestigated in view of the two-locus model of the H-2 complex. An attempt will be made to determine whether the previously reported K and D asymmetry in antigen loss is a general phenomenon, and if so, what is its basis. Since the H-2 antigens are important cell surface markers which might be involved in cell-to-cell recognition, the study of their behavior during variant formation should provide an insight into the phenomenon of tumor progression.